Poxviral-Based Prostate-Specific Antigen Vaccine in Prostate Cancer

Abstract

TO THE EDITOR: In the March 1, 2010, issue of Journal of Clinical Oncology, Kantoff et al reported the results of a phase II randomized trial of a poxviral-based prostate-specific antigen vaccine (PROSTVAC) in metastatic castration-resistant prostate cancer. Eighty-two patients received PROSTVAC and 40 received control vectors. The primary end point was progression-free survival, which was similar in both groups (hazard ratio, 0.884; 95% CI, 0.568 to 1.375; P .6), but overall survival (OS) favored PROSTVAC arm (25.1 v 16.6 months). The authors conclude that PROSTVAC immunotherapy is associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS. Although these data merit further exploration, we have concerns about whether both study arms are comparable. First, the difference in median age (71.6 v 79 years), percentage of lymph node involvement only (9.8% v 0%), and median survival estimated by Halabi nomogram may favor the PROSTVAC arm. Second, as Kantoff et al point out, the lack of treatment data after initial progression limits the interpretation of the survival result. PROSTVAC plus subsequent treatment improved in 3 months the survival predicted by Halabi. In the control arm, OS is reduced by 4 months as estimated by the Halabi nomogram. Half of the patients in the control arm received PROSTVAC as second-line treatment. An interesting question is whether a higher percentage of patients in the PROSTVAC arm received second-line docetaxel, obtaining a benefit in survival. Third, Kantoff et al mentioned that only docetaxel has been shown to affect survival in metastatic prostate cancer, by approximately 3 months. In the TAX 327 study, an OS of 19.2 months was reported in the every-3-weeks docetaxel arm. Nevertheless, patients included in the TAX 327 had an disfavorable prognosis when compared with the PROSTVAC study. Patients in TAX 327 were more symptomatic with a higher median prostate-specific antigen, Eastern Cooperative Oncology Group performance status of 2 was permitted, and 30% of patients had a Gleason score of 8 to 10. In a retrospective subanalysis of 110 minimally symptomatic patients, Berthold et al reported an OS of 28.4, 25.9, and 22 months for docetaxel every 3 weeks, docetaxel every week, or mitoxantrone, respectively. These differences did not reach statistical significance as a result of the small number of patients, and the results should be interpreted with caution. These data suggest than docetaxel should offer similar results to PROSTVAC in this population and should be the control arm in a phase III study. We agree with Kantoff et al that their findings are regarded as hypothesis generating, but OS data should be interpreted with caution in the absence of treatment information after progression to PROSTVAC or placebo.